..Thus, FLIP, which normally prevents inappropriate apoptosis, may become a tumor progression factor. Strategies to overcome this FLIP-mediated blockade of programmed cell death in tumors might become useful for positive prognoses...

..Third, the TRAIL death receptors can activate the NFkappaB pathway. This chapter summarizes basic knowledge regarding the understanding of the NFkappaB pathway and focuses on its multiple roles in TRAIL signaling...

..Some of the activities of the individual TRAF family members may be redundant although transgenic knockout animal models have already shown that crucial signaling pathways for single TRAF molecules in vivo can be defined...

Tumor necrosis factor signaling

H WajantInstitute of Cell Biology and Immunology, University of Stuttgart, Allmandring, GermanyCell Death Differ 10:45-65. 2003

..In particular, the multiple facets of crosstalk between the various signalling pathways engaged by TNF will be addressed...

..This review is focused on the non-apoptotic functions of the FasL/Fas system. In particular, the similarities and differences of the molecular mechanisms of apoptotic and non-apoptotic Fas signaling are addressed...

..We conclude that antibody targeting-dependent activation can be used to design selective therapeutics derived of those ligands of the TNF family that are biologically inactive in their soluble form...

..In accordance with this reasoning, the lower signaling capability of homotrimeric lymphotoxin, compared with TNF, correlates with a lower stability of the lymphotoxin-TNF-R1 complex at 37 degrees C...

I WatermannInstitute of Cell Biology and Immunology, University of Stuttgart, Stuttgart, GermanyCell Death Differ 14:765-74. 2007

..In a xenotransplantation tumor model, local application of the prodrug reduced the growth of target antigen-expressing, but not antigen-negative tumor cells, verifying targeted CD95L prodrug activation in vivo...

..This chapter focuses on the relevance of CD95L/FasL and TRAIL for the tumour surveillance function of natural killer cells and cytotoxic T-cells and discuss current concepts of utilizing these ligands in tumour therapy...

Role of caspases in CD95L- and TRAIL-induced non-apoptotic signalling in pancreatic tumour cells

..Overexpression of FLIP(L) and FLIP(S) inhibited Fas- as well as TRAIL-mediated NF-kappaB activation and apoptosis induction in IFN-gamma-primed cells suggesting that both responses are coregulated at the level of the DISC...

The extracellular domains of FasL and Fas are sufficient for the formation of supramolecular FasL-Fas clusters of high stability

..Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level...

..The expression of the cellular FLICE-like inhibitory protein (cFLIP) is regarded as a major cause of TRAIL resistance. We therefore analyzed the usefulness of targeting FLIP to sensitize tumor cells for TRAIL-induced apoptosis...

Caspase-mediated cleavage converts the tumor necrosis factor (TNF) receptor-associated factor (TRAF)-1 from a selective modulator of TNF receptor signaling to a general inhibitor of NF-kappaB activation

..Thus, tumor cell-derived TNFalpha plays a profound role in malignancy of PDAC, and inhibition of TNFalpha represents a promising therapeutic option particularly in adjuvant therapy after subtotal pancreatectomy...

Superior activity of fusion protein scFvRit:sFasL over cotreatment with rituximab and Fas agonists

..The principle described here for the first time, in which cell-surface antigen-mediated activation of Fas permits local activation of Fas in vivo, opens novel avenues for the use of Fas signaling in cancer therapy...

..Thus, the apoptosis-inducing action of interferons may not only rely on the well-established induction of TRAIL in effector cells but also on concomitant down-regulation of its antagonizing decoy receptor TRAILR4 in target cells...